U.S. patent application number 15/414465 was filed with the patent office on 2017-05-11 for acoustic manipulation of particles in standing wave fields.
This patent application is currently assigned to FLODESIGN SONICS, INC.. The applicant listed for this patent is FloDesign Sonics, Inc.. Invention is credited to Yuril Ilinskii, Bart Lipkens, Benjamin Ross-Johnsrud, Evgenia Zabolotskaya.
Application Number | 20170128857 15/414465 |
Document ID | / |
Family ID | 58667717 |
Filed Date | 2017-05-11 |
United States Patent
Application |
20170128857 |
Kind Code |
A1 |
Lipkens; Bart ; et
al. |
May 11, 2017 |
ACOUSTIC MANIPULATION OF PARTICLES IN STANDING WAVE FIELDS
Abstract
A method for separating a second fluid or a particulate from a
host fluid is disclosed. The method includes flowing the mixture
through an acoustophoretic device comprising an acoustic chamber,
an ultrasonic transducer, and a reflector. The transducer includes
a piezoelectric material driven by a voltage signal to create a
multi-dimensional acoustic standing wave in the acoustic chamber. A
voltage signal is sent to drive the ultrasonic transducer in a
displacement profile that is a superposition of a combination of
different mode shapes that are the same order of magnitude to
create the multi-dimensional acoustic standing wave in the acoustic
chamber such that the second fluid or particulate is continuously
trapped in the standing wave, and then agglomerates, aggregates,
clumps, or coalesces together, and subsequently rises or settles
out of the host fluid due to buoyancy or gravity forces, and exits
the acoustic chamber.
Inventors: |
Lipkens; Bart; (Hampden,
MA) ; Ross-Johnsrud; Benjamin; (Springfield, MA)
; Zabolotskaya; Evgenia; (Austin, TX) ; Ilinskii;
Yuril; (Austin, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
FloDesign Sonics, Inc. |
Wilbraham |
MA |
US |
|
|
Assignee: |
FLODESIGN SONICS, INC.
|
Family ID: |
58667717 |
Appl. No.: |
15/414465 |
Filed: |
January 24, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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15161108 |
May 20, 2016 |
9550134 |
|
|
15414465 |
|
|
|
|
62163994 |
May 20, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B06B 1/0276 20130101;
B01D 17/00 20130101; B06B 1/0674 20130101; H04L 2012/4026 20130101;
C02F 1/32 20130101; C12M 47/02 20130101; H04L 12/40032 20130101;
B01D 21/0084 20130101; B01D 43/00 20130101; B01D 21/283 20130101;
B01D 17/0202 20130101 |
International
Class: |
B01D 21/28 20060101
B01D021/28; H01L 41/187 20060101 H01L041/187; B06B 1/06 20060101
B06B001/06; B06B 1/20 20060101 B06B001/20; B01D 21/00 20060101
B01D021/00; C12M 1/00 20060101 C12M001/00 |
Claims
1. A device for separating a second fluid or a particulate from a
host fluid, comprising: an acoustic chamber including at least one
inlet and at least one outlet; at least one ultrasonic transducer
coupled to the acoustic chamber to permit generation of an acoustic
wave therein, the at least one ultrasonic transducer including a
piezoelectric material configured to be driven in a displacement
profile that is a superposition of a combination of different modes
that are the same order of magnitude to create a multi-dimensional
acoustic standing wave in the acoustic chamber; and a reflector
across the acoustic chamber from the at least one ultrasonic
transducer.
2. The device of claim 1, wherein the different modes have peaks
within a frequency interval between resonance frequencies of planar
standing waves.
3. The device of claim 1, wherein the combination of different
modes is at least two of modes (1, 1); (1, 3); (1, 5); (3, 3); (3,
5); and (5, 5).
4. The device of claim 1, wherein the piezoelectric material is
configured to vibrate to create an acoustic pressure profile in the
acoustic chamber in a direction that is orthogonal to a direction
of propagation of the acoustic standing wave, the pressure profile
including multiple maxima and minima.
5. The device of claim 1, wherein the at least one ultrasonic
transducer comprises: a housing with a top end, a bottom end, and
an interior volume; and a piezoelectric element at the bottom end
of the housing that includes an exposed exterior surface and an
interior surface, the piezoelectric element being able to vibrate
when driven by a voltage signal.
6. The device of claim 5, wherein a backing layer contacts the
interior surface of the piezoelectric element, the backing layer
being made of a substantially acoustically transparent material,
and wherein (i) the substantially acoustically transparent material
is balsa wood, cork, or foam; or (ii) wherein the substantially
acoustically transparent material has a thickness of up to 1 inch,
or (iii) wherein the substantially acoustically transparent
material is in the form of a lattice.
7. The device of claim 5, wherein an exterior surface of the
piezoelectric element is covered by a wear surface material with a
thickness of a half wavelength or less, the wear surface material
being a urethane, epoxy, or silicone coating.
8. The device of claim 5, wherein the piezoelectric element is free
of a backing layer or a wear layer.
9. The device of claim 1, wherein the reflector includes a
non-planar surface.
10. The device of claim 1, wherein the multi-dimensional acoustic
standing wave is generated in the acoustic chamber normal to a
direction of flow therethrough.
11. The device of claim 1, wherein the reflector is a piezoelectric
acoustic transducer.
12. A device for separating a second fluid or a particulate from a
host fluid, comprising: an acoustic chamber including at least one
inlet and at least one outlet; at least one ultrasonic transducer
coupled to the acoustic chamber to permit generation of an acoustic
wave therein, the at least one ultrasonic transducer including a
piezoelectric material configured to be driven at a frequency of
excitation that excites multiple modes at the same time, to create
a multi-dimensional acoustic standing wave in the acoustic
chamber.
13. The device of claim 12, wherein the multiple modes are of the
same order of magnitude.
14. The device of claim 12, wherein the multiple modes have peaks
within a frequency interval between resonance frequencies of planar
standing waves.
15. The device of claim 14, wherein the multiple modes have peaks
within a 50% portion of a frequency interval between resonance
frequencies of the planar standing waves.
16. The device of claim 12, wherein the multiple modes include at
least two modes selected from the group consisting of modes (1, 1);
(1, 3); (1, 5); (3, 3); (3, 5); and (5, 5).
17. The device of claim 12, further comprising a reflector located
opposite from the at least one ultrasonic transducer.
18. A device for separating a second fluid or a particulate from a
host fluid, comprising: an acoustic chamber including at least one
inlet and at least one outlet; at least one ultrasonic transducer
coupled to the acoustic chamber to permit generation of an acoustic
wave therein, the at least one ultrasonic transducer including a
piezoelectric material configured to be driven so that the
piezoelectric material vibrates in higher order modes of the
general formula (m, n), wherein m and n are independently 1 or
greater, to create a multi-dimensional acoustic standing wave in
the acoustic chamber; and a reflector located opposite to the at
least one ultrasonic transducer.
19. The device of claim 18, wherein the higher order modes are of
the same order of magnitude.
20. The device of claim 18, wherein the higher order modes include
at least two modes selected from the group consisting of modes (3,
3); (3, 5); and (5, 5).
21. A device for separating a second fluid or a particulate from a
host fluid, comprising: an acoustic chamber including at least one
inlet and at least one outlet; at least one ultrasonic transducer
coupled to the acoustic chamber to permit generation of an acoustic
wave therein, the at least one ultrasonic transducer including a
piezoelectric material configured to be driven in a displacement
profile that is a superposition of a combination of different modes
to create a multi-dimensional acoustic standing wave in the
acoustic chamber; where the multidimensional acoustic standing wave
is the result of the perturbation of a PZT material having
characteristics of a 33 orientation where the piezoelectric
elements are characterized by independent .lamda. values,
independent e values, and independent .epsilon. values such that,
in a resonant cavity with an acoustic standing wave, the electrical
boundary conditions are defined by the following equations:
.phi.(x,y,z=d.sub.z)=.SIGMA..sub.n,mV.sub.n,m cos k.sub.xnx cos
k.sub.ymy .phi.(x,y,z=0)=0 where V is the voltage amplitude, n is
the periodic index, and m is the periodic index for the (n,m) mode
of interest; and a reflector located across the acoustic chamber
from the at least one ultrasonic transducer.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent
application Ser. No. 15/161,108, filed on May 20, 2016, which
claims priority to U.S. Provisional Patent Application Ser. No.
62/163,994, filed on May 20, 2015, the disclosures of which are
hereby fully incorporated by reference in their entireties.
BACKGROUND
[0002] The subject matter described herein relates to the use of
ultrasonically generated acoustic standing waves to achieve
trapping, concentration, and separation of suspended-phase
components and thereby remove such contaminants from a fluid medium
such as water.
[0003] When particles are entrained or dispersed in a flowing
fluid, aggregation of the particles to form larger clumps is
typically due to some attraction or adhesion between the particles
or the addition of a flocculating agent that aids in attracting and
aggregating the particles. Attractive forces between the particles
may be ionic or physical entanglement.
[0004] Typically, after the clumps of particles are formed in the
fluid medium, a physical filtration process is utilized to separate
the aggregated, agglomerated, flocculated or otherwise
process-formed particle clumps. Most of the work reported in the
literature for particle removal from water involves replaceable
filter units consisting generally of packed cartridges, filter
membranes, or special filter papers. If the separation process is a
filter separation process, the physical filter media and the clumps
of particles that have been separated from the fluid media are
typically discarded, thus creating additional waste and increasing
costs. Also, with the use of this physical filtration process, the
yield of the filtrate is lessened, as some of it is used to
saturate the filtering material. Further, as the filter fills up,
filtration capacity is reduced, and using such filters may impose
periodic stopping to remove the filter and obtain the particles
trapped thereon. Finally, though particles over 10 micrometers can
typically be captured by these techniques, smaller particles, such
as bacterial spores in the size range of 1 micrometer, are
typically not captured with sufficient efficiency.
[0005] Thus, methods are sought where continuous filtration may be
carried out. Such continuous methods would be useful in various
filtration applications, such as the filtering of oil from water,
components from blood, tailings from water in tailing ponds, and,
generally, particles from a fluid stream and immiscible or
emulsified fluids from a fluid stream.
[0006] Acoustophoresis is the separation of particles and secondary
fluids from a primary or host fluid using high intensity acoustic
standing waves, and without the use of membranes or physical size
exclusion filters. It has been known that high intensity standing
waves of sound can exert forces on particles in a fluid when there
is a differential in both density and/or compressibility, otherwise
known as the acoustic contrast factor. The pressure profile in a
standing wave contains areas of local minimum pressure amplitudes
at its nodes and local maxima at its anti-nodes. Depending on the
density and compressibility of the particles, they will be trapped
at the nodes or anti-nodes of the standing wave. Generally, the
higher the frequency of the standing wave, the smaller the
particles that can be trapped due the pressure of the standing
wave.
[0007] In conventional acoustophoretic devices, planar acoustic
standing waves, with resonance frequencies of n*c/2L, where n is an
integer, c is the speed of sound of the fluid, and L is the length
of the acoustic resonator resonator or the length of the standing
wave, have been used to accomplish the separation process. However,
a single planar wave tends to trap the particles or secondary fluid
in a manner such that they can only be separated from the primary
fluid by turning off the planar standing wave. This does not allow
for continuous operation. Also, the amount of power that is needed
to generate the acoustic planar standing wave tends to heat the
primary fluid through waste energy.
[0008] Conventional acoustophoresis devices have thus had limited
efficacy due to several factors including heat generation, use of
planar standing waves, limits on fluid flow, and the inability to
capture different types of materials. It would therefore be
desirable to provide systems and methods of generating optimized
particle clusters to improve gravity separation and collection
efficiency. Improved acoustophoresis devices using improved fluid
dynamics would also be desirable, so the acoustophoresis can be a
continuous process.
BRIEF DESCRIPTION
[0009] The present disclosure relates, in various embodiments, to
acoustophoretic devices and methods of separating a second fluid or
a particulate from a host fluid. Briefly, a superposition of
multi-dimensional acoustic standing waves is used to continuously
trap the second fluid or particulate, which then agglomerates,
aggregates, clumps, or coalesces together, and subsequently rises
or settles out of the host fluid due to buoyancy or gravity forces,
and exits the acoustic chamber.
[0010] Method disclosed herein for separating a second fluid or a
particulate from a host fluid comprise flowing a mixture of the
host fluid and the second fluid or particulate through an
acoustophoretic device. The acoustophoretic device comprises an
acoustic chamber having at least one inlet and at least one outlet;
at least one ultrasonic transducer located on a wall of the
acoustic chamber, the at least one ultrasonic transducer including
a piezoelectric material driven by a voltage signal to create a
superposition of multi-dimensional acoustic standing waves in the
acoustic chamber; and a reflector located on a wall on the opposite
side of the acoustic chamber from the at least one ultrasonic
transducer. The method further comprises sending a voltage signal
to drive the at least one ultrasonic transducer in a displacement
profile that is a superposition of a combination of different modes
(such as planar, fundamental, and/or higher order mode shapes) that
are the same order of magnitude to create the multi-dimensional
acoustic standing wave in the acoustic chamber such that the second
fluid or particulate is continuously trapped in the standing wave,
and then agglomerates, aggregates, clumps, or coalesces together,
and subsequently rises or settles out of the host fluid due to
buoyancy or gravity forces, and exits the acoustic chamber.
[0011] Mode (1, 1) is known as the fundamental mode. The
fundamental and higher order mode shapes may have peaks within
0.005 megahertz (MHz) of each other. The higher order mode shapes
may include modes (1, 3); (1, 5); (3, 3); (3, 5); and (5, 5). In
certain embodiments, the higher order modes may include modes up to
(25, 25) and higher. The different modes may have peaks within a
frequency interval between resonance frequencies of planar standing
waves.
[0012] A frequency of excitation of the piezoelectric material can
be changed or dithered over a small interval, exciting the
piezoelectric material in multiple higher order modes, and then
cycling the frequency back through lower modes of the piezoelectric
material, thereby allowing for various multi-dimensional wave
shapes, along with a single piston mode shape, to be generated over
a designated time. In other embodiments, a frequency of excitation
of the piezoelectric material is a fixed frequency excitation where
a weighted combination of several modes contribute to the overall
displacement profile of the piezoelectric element. The
piezoelectric material may be configured to vibrate to create an
acoustic pressure profile in the acoustic chamber in a direction
that is orthogonal to a direction of propagation of the acoustic
standing wave, the pressure profile including multiple maxima and
minima.
[0013] In particular embodiments, the multi-dimensional standing
wave results in an acoustic radiation force having an axial force
component and a lateral force component that are the same order of
magnitude. The multi-dimensional acoustic standing wave can be
generated in the acoustic chamber normal to a direction of flow
therethrough. The piezoelectric material can vibrate to create a
pressure profile across the surface of the flowing mixture, the
pressure profile having multiple maxima and minima. Hot spots in
the mixture can be generated that are located at a minimum of the
acoustic radiation potential. The voltage signal can have a
sinusoidal, square, sawtooth, triangle, or pulsed waveform. The
voltage signal can have a frequency of 100 kHz to 10 MHz. The
voltage signal can be driven with amplitude or frequency modulation
start/stop capability to eliminate acoustic streaming. The
reflector may have a non-planar surface.
[0014] In some implementations, a multi-dimensional acoustic
standing wave is generated between two or more acoustic transducers
arranged to direct a generated acoustic wave toward each other. For
example, the reflector may be replaced by an acoustic transducer
that is capable of generating a multi-dimensional standing wave.
The combination of transducers contributes to generating and
reflecting acoustic waves to create a multi-dimensional standing
wave. For example, the acoustic waves generated by the transducers
can arranged to constructively and/or destructively interfere with
each other to form a multi-dimensional standing wave.
[0015] In some implementations, an acoustic transducer pair, or
acoustic transducer/reflector pair are configured to operate in
multi-mode. Multi-mode operation provides for a number of modes
being present at a certain operating point, such as a frequency
operating point, for example. Multi-mode operation may occur at
operating points between instances of single-mode operation. During
multi-mode operation, a primarily dominant mode may be present, in
addition to one or more secondary modes. The superposition of modes
may contribute to forming a multi-dimensional acoustic standing
wave, with lateral as well as axial acoustic radiation forces. The
primary and secondary modes may vary depending on selected
operating points, for example. When an acoustic transducer
generates an acoustic wave that is reflected back to the transducer
to create a standing wave, the reflected wave can act as a load on
the acoustic transducer. The loading of the transducer, from a
reflected wave or other sources of loading, such as a second
acoustic transducer acoustically coupled through a fluid, can
influence multi-mode operation. For example, a transducer load may
change the frequency at which a given mode becomes dominant or
peaks. A desired operating point for multi-mode operation, and the
characteristics of the different modes, may thus be impacted by
loading.
[0016] In certain constructions, the at least one ultrasonic
transducer may comprise: a housing having a top end, a bottom end,
and an interior volume; and a piezoelectric element at the bottom
end of the housing having an exposed exterior surface and an
interior surface, the piezoelectric element being able to vibrate
when driven by a voltage signal. A backing layer can contact the
interior surface of the piezoelectric element, the backing layer
being made of a substantially acoustically transparent material.
The substantially acoustically transparent material may be balsa
wood, cork, or foam. The substantially acoustically transparent
material may have a thickness of up to 1 inch. The substantially
acoustically transparent material may be in the form of a lattice.
An exterior surface of the piezoelectric element can be covered by
a wear surface material with a thickness of a half wavelength or
less, the wear surface material being a urethane, epoxy, or
silicone coating. In some embodiments, the piezoelectric element
has no backing layer or wear layer. The piezoelectric element can
be a crystalline, semi-crystalline, or non-crystalline.
[0017] In the methods according to the present disclosure, the
mixture of the second fluid or particulate can flow vertically
downwards, and the second fluid or particulate can float upward to
a collection duct. In alternative embodiments, the mixture can flow
vertically upwards, and the second fluid or particulate can sink
down to a collection duct. The particulate may be Chinese hamster
ovary (CHO) cells, NS0 hybridoma cells, baby hamster kidney (BHK)
cells, or human cells.
[0018] In particular embodiments, the acoustic standing wave may be
a multi-dimensional acoustic standing wave. Examples of such
multi-dimensional acoustic standing waves can be found in commonly
owned U.S. Pat. No. 9,228,183, the entire contents of which are
hereby fully incorporated by reference. In other embodiments, the
acoustic standing wave can be a planar acoustic standing wave.
Further yet, in particular embodiments, the acoustic standing wave
may be a combination of a planar acoustic standing wave and a
multidimensional acoustic standing wave, where the planar acoustic
standing wave and multidimensional acoustic standing wave are
super-positioned on each other.
[0019] Also disclosed herein are devices for separating a second
fluid or a particulate from a host fluid, comprising: an acoustic
chamber including at least one inlet and at least one outlet; at
least one ultrasonic transducer coupled to the acoustic chamber to
permit generation of an acoustic wave therein, the at least one
ultrasonic transducer including a piezoelectric material configured
to be driven so that the piezoelectric material vibrates in higher
order modes of the general formula (m, n), wherein m and n are
independently 1 or greater (or 3 or greater), to create a
multi-dimensional acoustic standing wave in the acoustic chamber;
and a reflector located opposite to the at least one ultrasonic
transducer. The higher order modes may be of the same order of
magnitude. The higher order modes can include at least two modes
selected from the group consisting of modes (3, 3); (3, 5); and (5,
5).
[0020] Also described herein are devices for separating a second
fluid or a particulate from a host fluid, comprising: an acoustic
chamber including at least one inlet and at least one outlet; at
least one ultrasonic transducer coupled to the acoustic chamber to
permit generation of an acoustic wave therein, the at least one
ultrasonic transducer including a piezoelectric material configured
to be driven in a displacement profile that is a superposition of a
combination of different modes to create a multi-dimensional
acoustic standing wave in the acoustic chamber; where the
multidimensional acoustic standing wave is the result of the
perturbation of a PZT material having characteristics of a 33
orientation where the piezoelectric elements are characterized by
independent .lamda. values, independent e values, and independent
.epsilon. values such that, in a resonant cavity with an acoustic
standing wave, the electrical boundary conditions are defined by
the following equations:
.phi.(x,y,z=d.sub.z)=.SIGMA..sub.n,mV.sub.n,m cos k.sub.xnx cos
k.sub.ymy
.phi.(x,y,z=0)=0
where V is the voltage amplitude, n is the periodic index, and m is
the periodic index for the (n,m) mode of interest; and a reflector
located across the acoustic chamber from the at least one
ultrasonic transducer.
[0021] These and other non-limiting characteristics are more
particularly described below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] The following is a brief description of the drawings, which
are presented for the purposes of illustrating the exemplary
embodiments disclosed herein and not for the purposes of limiting
the same.
[0023] FIG. 1 is a graph showing the relationship of the acoustic
radiation force, gravity/buoyancy force, and Stokes' drag force to
particle size. The horizontal axis is in microns (.mu.m) and the
vertical axis is in Newtons (N).
[0024] FIG. 2 illustrates a general configuration of a
piezoelectric element separated from a reflective boundary layer by
a water layer.
[0025] FIG. 3 presents the traditional approach of utilizing a
transducer and reflector to generate a planar standing wave to
create loosely packed planes of particles in an acoustic chamber.
Three views are seen: a reflector view, a system view, and an
isometric view.
[0026] FIG. 4 presents a new approach according to the present
disclosure of utilizing a transducer and reflector to generate a
multi-dimensional acoustic standing wave to create tightly packed
cluster of particles in an acoustic chamber. Three views are seen:
a reflector view, a system view, and an isometric view.
[0027] FIG. 5 is a diagram illustrating an acoustophoretic
separation method according to the present disclosure for a second
fluid or particle less dense than a host fluid.
[0028] FIG. 6 is a diagram illustrating an acoustophoretic
separation method according to the present disclosure for a second
fluid or particle denser than a host fluid.
[0029] FIG. 7 is a cross-sectional diagram of a conventional
ultrasonic transducer.
[0030] FIG. 8 is a cross-sectional diagram of an ultrasonic
transducer according to the present disclosure. An air gap is
present within the transducer, and no backing layer or wear plate
is present.
[0031] FIG. 9 is a cross-sectional diagram of an ultrasonic
transducer according to the present disclosure. An air gap is
present within the transducer, and a backing layer and wear plate
are present.
[0032] FIG. 10 shows the In-Plane and Out-of-Plane displacement of
a piezoelectric crystal where composite waves are present.
[0033] FIG. 11 presents analytical results for the displacement
response of a 25.4.times.25.4.times.1 mm PZT-8 piezoelectric
crystal with a radiating water layer.
[0034] FIG. 12 presents analytical results for the displacement
response of a 25.4.times.25.4.times.1 mm PZT-8 piezoelectric
crystal with a 25.4 mm fluid chamber terminated by an acoustic
reflector.
[0035] FIG. 13 presents a two-dimensional COMSOL numerical model of
the piezoelectric equations according to the present
disclosure.
[0036] FIG. 14 presents numerical results for the displacement
response of a 25.4.times.25.4.times.1 mm PZT-8 piezoelectric
crystal with a 25.4 mm fluid chamber terminated by an acoustic
reflector.
[0037] FIG. 15 presents numerical results for the current response
of a 25.4.times.25.4.times.1 mm PZT-8 piezoelectric crystal with a
25.4 mm fluid chamber terminated by an acoustic reflector.
[0038] FIG. 16 presents experimental results for the current
response of a 25.4.times.25.4.times.1 mm PZT-8 piezoelectric
crystal operated with a 30 kHz frequency sweep with a 25.4 mm fluid
chamber terminated by an acoustic reflector.
DETAILED DESCRIPTION
[0039] The present disclosure may be understood more readily by
reference to the following detailed description of desired
embodiments and the examples included therein. In the following
specification and the claims which follow, reference will be made
to a number of terms which shall be defined to have the following
meanings.
[0040] Although specific terms are used in the following
description for the sake of clarity, these terms are intended to
refer only to the particular structure of the embodiments selected
for illustration in the drawings, and are not intended to define or
limit the scope of the disclosure. In the drawings and the
following description below, it is to be understood that like
numeric designations refer to components of like function.
[0041] The singular forms "a," "an," and "the" include plural
referents unless the context clearly dictates otherwise.
[0042] The term "comprising" is used herein as requiring the
presence of the named component and allowing the presence of other
components. The term "comprising" should be construed to include
the term "consisting of", which allows the presence of only the
named component, along with any impurities that might result from
the manufacture of the named component.
[0043] Numerical values should be understood to include numerical
values which are the same when reduced to the same number of
significant figures and numerical values which differ from the
stated value by less than the experimental error of conventional
measurement technique of the type described in the present
application to determine the value.
[0044] All ranges disclosed herein are inclusive of the recited
endpoint and independently combinable (for example, the range of
"from 2 grams to 10 grams" is inclusive of the endpoints, 2 grams
and 10 grams, and all the intermediate values). The endpoints of
the ranges and any values disclosed herein are not limited to the
precise range or value; they are sufficiently imprecise to include
values approximating these ranges and/or values.
[0045] The modifier "about" used in connection with a quantity is
inclusive of the stated value and has the meaning dictated by the
context. When used in the context of a range, the modifier "about"
should also be considered as disclosing the range defined by the
absolute values of the two endpoints. For example, the range of
"from about 2 to about 10" also discloses the range "from 2 to 10."
The term "about" may refer to plus or minus 10% of the indicated
number. For example, "about 10%" may indicate a range of 9% to 11%,
and "about 1" may mean from 0.9-1.1.
[0046] It should be noted that many of the terms used herein are
relative terms. For example, the terms "upper" and "lower" are
relative to each other in location, i.e. an upper component is
located at a higher elevation than a lower component in a given
orientation, but these terms can change if the device is flipped.
The terms "inlet" and "outlet" are relative to a fluid flowing
through them with respect to a given structure, e.g. a fluid flows
through the inlet into the structure and flows through the outlet
out of the structure. The terms "upstream" and "downstream" are
relative to the direction in which a fluid flows through various
components, i.e. the flow fluids through an upstream component
prior to flowing through the downstream component. It should be
noted that in a loop, a first component can be described as being
both upstream of and downstream of a second component.
[0047] The terms "horizontal" and "vertical" are used to indicate
direction relative to an absolute reference, i.e. ground level.
However, these terms should not be construed to require structures
to be absolutely parallel or absolutely perpendicular to each
other. For example, a first vertical structure and a second
vertical structure are not necessarily parallel to each other. The
terms "top" and "bottom" or "base" are used to refer to surfaces
where the top is always higher than the bottom/base relative to an
absolute reference, i.e. the surface of the earth. The terms
"upwards" and "downwards" are also relative to an absolute
reference; upwards is always against the gravity of the earth.
[0048] The term "parallel" should be construed in its lay sense of
two surfaces that maintain a generally constant distance between
them, and not in the strict mathematical sense that such surfaces
will never intersect when extended to infinity.
[0049] The present application refers to "the same order of
magnitude." Two numbers are of the same order of magnitude if the
quotient of the larger number divided by the smaller number is a
value of at least 1 and less than 10.
[0050] Acoustophoresis is the separation of particles and secondary
fluids from a primary or host fluid using high-intensity acoustic
standing waves, and without the use of membranes or physical size
exclusion filters. It has been known that high intensity standing
waves of sound can exert forces on particles in a fluid when there
is a differential in both density and/or compressibility, otherwise
known as the acoustic contrast factor. The pressure profile in a
standing wave contains areas of local minimum pressure amplitudes
at its nodes and local maxima at its anti-nodes. Depending on the
density and compressibility of the particles, they will be trapped
at the nodes or anti-nodes of the standing wave. Generally, the
higher the frequency of the standing wave, the smaller the
particles that can be trapped due the pressure of the standing
wave.
[0051] When acoustic standing waves propagate in liquids, the fast
oscillations may generate a non-oscillating force on particles
suspended in the liquid or on an interface between liquids. This
force is known as the acoustic radiation force. The force
originates from the non-linearity of the propagating wave. As a
result of the non-linearity, the wave is distorted as it propagates
and the time-averages are nonzero. By serial expansion (according
to perturbation theory), the first non-zero term will be the
second-order term, which accounts for the acoustic radiation force.
The acoustic radiation force on a particle, or a cell, in a fluid
suspension is a function of the difference in radiation pressure on
either side of the particle or cell. The physical description of
the radiation force is a superposition of the incident wave and a
scattered wave, in addition to the effect of the non-rigid particle
oscillating with a different speed compared to the surrounding
medium thereby radiating a wave. The following equation presents an
analytical expression for the acoustic radiation force on a
particle, or cell, in a fluid suspension in a planar standing
wave.
F R = 3 .pi. P 0 2 V P .beta. m 2 .lamda. .PHI. ( .beta. , .rho. )
sin ( 2 kx ) ( 1 ) ##EQU00001##
where .beta..sub.m is the compressibility of the fluid medium,
.rho. is density, .phi. is acoustic contrast factor, V.sub.p is
particle volume, .lamda. is wavelength, k is 2.pi./.lamda., P.sub.0
is acoustic pressure amplitude, x is the axial distance along the
standing wave (i.e., perpendicular to the wave front), and
.PHI. ( .beta. , .rho. ) = 5 .rho. .rho. - 2 .rho. m 2 .rho. .rho.
+ .rho. m - .beta. .rho. .beta. m ##EQU00002##
where .rho..sub.p is the particle density, .rho..sub.m is the fluid
medium density, .beta..sub.p is the compressibility of the
particle, and .beta..sub.m is the compressibility of the fluid
medium.
[0052] For a multi-dimensional standing wave, the acoustic
radiation force is a three-dimensional force field, and one method
to calculate the force is Gor'kov's method, where the primary
acoustic radiation force F.sub.R is defined as a function of a
field potential U, F.sub.V=-.gradient.(U), where the field
potential U is defined as
U = 4 3 .pi. R p 3 [ p 2 ( x , y , z ) 2 .rho. f c f 2 f 1 - 3
.rho. f v 2 ( x , y , z ) 4 f 2 ] ##EQU00003##
and f.sub.1 and f.sub.2 are the monopole and dipole contributions
defined by
f 1 = 1 - 1 .LAMBDA..sigma. 2 f 2 = 2 ( .LAMBDA. - 1 ) 2 .LAMBDA. +
1 where ##EQU00004## .sigma. = c p c f .LAMBDA. = p p p f .beta. f
= 1 .rho. f c f 2 ##EQU00004.2##
where .rho. is the acoustic pressure, u is the fluid particle
velocity, .LAMBDA. is the ratio of cell density .rho..sub.p to
fluid density .rho..sub.f, .sigma. is the ratio of cell sound speed
c.sub.p to fluid sound speed c.sub.f, V.sub.o is the volume of the
cell, and < > indicates time averaging over the period of the
wave.
[0053] Gork'ov's model is for a single particle in a standing wave
and is limited to particle sizes that are small with respect to the
wavelength of the sound fields in the fluid and the particle. It
also does not take into account the effect of viscosity of the
fluid and the particle on the radiation force. As a result, this
model cannot be used for macro-scale ultrasonic separators since
particle clusters can grow quite large.
[0054] FIG. 1 is a log-log graph (logarithmic y-axis, logarithmic
x-axis) that shows the scaling of the acoustic radiation force,
fluid drag force, and buoyancy force with particle radius.
Calculations are done for a typical mammalian cell used in
experiments. In the experiment, the mammalian cell had a density
(.rho..sub.p) of 1,050 kg/m.sup.3 and a cell sound speed (c.sub.p)
of 1,550 m/s. The fluid in which the particle was flowed was water
having a density (.rho..sub.w) of 1000 kg/m.sup.3, a fluid sound
speed (c.sub.f) of 1500 m/s, and a flow rate (v.sub.f) of 4 cm/min.
The experiment used 33 PZT-8 ultrasonic transducers driven at a
frequency (f) of 2.2 MHz at a pressure (p) of 1 MPa. As explained
above, the gravity/buoyancy force is a particle volume dependent
force, and is therefore negligible for particle sizes on the order
of micron, but grows, and becomes significant for particle sizes on
the order of hundreds of microns. The fluid drag force scales
linearly with fluid velocity, and therefore typically exceeds the
buoyancy force for micron sized particles, but is negligible for
larger sized particles on the order of hundreds of microns. The
acoustic radiation force scaling is different. When the particle
size is small, Gor'kov's equation is accurate and the acoustic
trapping force scales with the volume of the particle. Eventually,
when the particle size grows, the acoustic radiation force no
longer increases with the cube of the particle radius, and will
rapidly vanish at a certain critical particle size. For further
increases of particle size, the radiation force increases again in
magnitude but with opposite phase (not shown in the graph). This
pattern repeats for increasing particle sizes.
[0055] Initially, when a suspension is flowing through the system
with primarily small micron sized particles, it is necessary for
the acoustic radiation force to balance the combined effect of
fluid drag force and buoyancy force for a particle to be trapped in
the standing wave. In FIG. 1, this happens for a particle size of
about 3.5 micron, labeled as R.sub.c1. The graph then indicates
that all larger particles will be trapped as well. Therefore, when
small particles are trapped in the standing wave, particles
coalescence/clumping/aggregation/agglomeration takes place,
resulting in continuous growth of effective particle size. As the
particle size grows, the acoustic radiation force reflects off the
particle, such that large particles will cause the acoustic
radiation force to decrease. Particle size growth continues until
the buoyancy force becomes dominant, which is indicated by a second
critical particle size, R.sub.c2, at which size the particles will
rise or sink, depending on their relative density with respect to
the host fluid. Thus, FIG. 1 explains how small particles can be
trapped continuously in a standing wave, grow into larger particles
or clumps, and then eventually will rise or settle out because of
increased buoyancy force.
[0056] A more complex and complete model than for acoustic
radiation forces that is not limited by particle size, like
Gork'ov's model, may be used. The models that were implemented in
the present disclosure are based on the theoretical work of Yurii
Ilinskii and Evgenia Zabolotskaya as described in AIP Conference
Proceedings, Vol. 1474-1, pp. 255-258 (2012). These models also
include the effect of fluid and particle viscosity, and therefore
are a more accurate calculation of the acoustic radiation force.
FIG. 2 shows a very general configuration of a piezoelectric
material with electrodes on its faces. One electrode is configured
as a periodic electric potential electrode, while the other
electrode is configured as a ground electrode. The piezoelectric
material is located opposite an acoustic reflector that provides a
reflective boundary condition. The reflector and piezoelectric
material are separated by a water layer. The general formulation of
the piezoelectric equations is:
- .rho..omega. 2 u i = .lamda. iklm .differential. 2 u l
.differential. x m .differential. x k = e jik .differential. 2
.PHI. .differential. x j .differential. x k ##EQU00005## 0 = e ikl
.differential. 2 u k .differential. x l .differential. x i - ik
.differential. 2 .PHI. .differential. x i .differential. x k
##EQU00005.2##
where p is the density, .omega. is the angular frequency, u is the
displacement tensor, .phi. is the electric field potential, .lamda.
is the elasticity tensor, e is the coupling tensor, and .epsilon.
is the permittivity tensor. Based on this general formulation, the
assumed solutions of the piezoelectric equations are:
u.sub.x= .sub.x sin(k.sub.xx)cos(k.sub.yy)e.sup.iKz u.sub.y= .sub.y
sin(k.sub.yy)cos(k.sub.xx)e.sup.iKz
u.sub.z= .sub.z cos(k.sub.xx)cos(k.sub.yy)e.sup.iKz .phi.={tilde
over (.phi.)} cos(k.sub.xx)cos(k.sub.yy)e.sup.iKz
where and {tilde over (.phi.)} are the complex amplitude and k and
K are the wave numbers of the piezoelectric element. For 33
oriented PZT-8 piezoelectric elements, there are five independent
.lamda. values, three independent e values, and two independent
.epsilon. values.
[0057] The mechanical boundary conditions are defined by the
following equations:
.sigma. zz ( d z ) = .lamda. 13 ( .differential. u x .differential.
x + .differential. u y .differential. y ) + .lamda. 33
.differential. u z .differential. z + e 33 .differential. .PHI.
.differential. z = 0 ##EQU00006## .sigma. xz ( d z ) = 1 2 .lamda.
55 ( .differential. u x .differential. z + .differential. u z
.differential. x ) + e 15 .differential. .PHI. .differential. x = 0
##EQU00006.2## .sigma. yz ( d z ) = 1 2 .lamda. 55 ( .differential.
u y .differential. z + .differential. u z .differential. y ) + e 15
.differential. .PHI. .differential. y = 0 ##EQU00006.3## .sigma. zz
( 0 ) = .lamda. 13 ( .differential. u x .differential. x +
.differential. u y .differential. y ) + .lamda. 33 .differential. u
z .differential. z + e 33 .differential. .PHI. .differential. z = -
p w ##EQU00006.4## .sigma. xz ( 0 ) = 1 2 .lamda. 55 (
.differential. u x .differential. z + .differential. u z
.differential. x ) + e 15 .differential. .PHI. .differential. x = 0
##EQU00006.5## .sigma. yz ( 0 ) = 1 2 .lamda. 55 ( .differential. u
y .differential. z + .differential. u z .differential. y ) + e 15
.differential. .PHI. .differential. y = 0 ##EQU00006.6## p w ( z =
0 ) = ip w .omega. 2 k w 2 - k x 2 - k y 2 1 + K R 2 ik x L 1 - K R
2 ik x L u z ( z = 0 ) ##EQU00006.7##
where .sigma. is the stress, d.sub.z is the thickness of the
piezoelectric element, p.sub.w is the acoustic pressure in water,
.rho..sub.w is the density of water, k.sub.w is the wave number in
water, K.sub.R is the reflection coefficient, and L is the length
of the water layer.
[0058] The electrical boundary conditions are defined by the
following equations:
.phi.(x,y,z=d.sub.z)=.SIGMA..sub.n,mV.sub.n,m cos k.sub.xnx cos
k.sub.ymy
.phi.(x,y,z=0)=0
where V is the voltage amplitude, n is the periodic index, and m is
the periodic index for the (n,m) mode of interest.
[0059] The acoustophoretic separation technology of the present
disclosure employs multi-dimensional ultrasonic acoustic standing
waves, planar acoustic standing waves or combinations, i.e.,
superpositions, of planar and multidimensional acoustic standing
waves (collectively referred to herein simple as acoustic standing
waves) to trap particles or a secondary fluid in a volume of fluid
containing said particles/secondary fluid.
[0060] FIG. 3 presents the traditional approach of utilizing a
transducer and reflector located opposite one another to generate a
planar standing wave therebetween. The left side of FIG. 3 presents
a view of the acoustic chamber as seen through the reflector, while
the middle picture of FIG. 3 presents a system view of the acoustic
chamber from above. As can be seen in FIG. 3, the generation of a
planar standing wave in an acoustic chamber results in the creation
of loosely packed planes of particles in the acoustic chamber,
typically corresponding to the pressure nodal planes for particles
with positive acoustic contrast.
[0061] FIG. 4, on the other hand, presents a new approach of
utilizing a transducer and reflector located opposite one another
to generate a multi-dimensional acoustic standing wave
therebetween, or a superposition of multi-dimensional acoustic
standing waves. As with FIG. 3, the left side of FIG. 4 presents a
view of the acoustic chamber as seen through the reflector, while
the middle picture of FIG. 4 presents a system view of the acoustic
chamber from above. As can be seen in FIG. 4, the generation of a
multi-dimensional acoustic standing wave in an acoustic chamber
results in the creation of tightly packed clusters of particles in
the acoustic chamber, typically corresponding to the location of
the pressure nodes or anti-nodes in the standing wave depending on
acoustic contrast factor.
[0062] The particles or secondary fluid collect at the nodes or
anti-nodes of the acoustic standing wave, depending on the
particles' or secondary fluid's acoustic contrast factor relative
to the host fluid, forming clusters/clumps/agglomerates/coalesced
droplets that continuously fall out of the acoustic standing wave
when the clusters have grown to a size large enough to overcome the
holding force of the acoustic standing wave (e.g. by coalescence or
agglomeration) and the particle/secondary fluid density is higher
than the host fluid, or to rise out of the acoustic standing wave
when the particle/secondary fluid density is less than the host
fluid. The acoustic radiation force is proportional to the particle
volume (e.g. the cube of the radius) when the particle is small
relative to the wavelength. It is proportional to frequency and the
acoustic contrast factor. It also scales with acoustic energy (e.g.
the square of the acoustic pressure amplitude). For harmonic
excitation, the sinusoidal spatial variation of the force is what
drives the particles to the stable axial positions within the
standing waves. When the acoustic radiation force exerted on the
particles is stronger than the combined effect of fluid drag force
and buoyancy and gravitational force, the particle is trapped
within the acoustic standing wave field. This results in
concentration, agglomeration and/or coalescence of the trapped
particles. The strong lateral forces create rapid clustering of
particles. Micron-sized particles, e.g., bacteria, mammalian cells,
micro-algae, metal particles, yeast, fungi, lipids, oil droplets,
red blood cells, white blood cells, platelets, etc., can thus be
separated from the host fluid through enhanced gravitational
separation. For the case of a suspension with several different
particle sizes, it is possible by tuning of the system parameters
to settle out the group of particles that are larger in size
whereas the group of particles smaller in size can be kept in
suspension. These two layers can then be harvested separately. A
repeated process can then be used to fractionate groups of
different sized particles according to size. In this regard, the
multi-dimensional acoustic standing waves generated by each
transducer can be of different frequencies.
[0063] One specific application for the acoustophoresis device is
in the processing of bioreactor materials. It is important to be
able to separate relatively larger cells and cell debris from the
expressed materials that are in the host fluid. The expressed
materials are composed of biomolecules such as recombinant proteins
or monoclonal antibodies, and are the desired product to be
recovered. Through the use of acoustophoresis, the separation of
the cells and cell debris is very efficient and leads to very
little loss of the expressed materials. This is an improvement over
current filtration processes (depth filtration, tangential flow
filtration, and the like), which show limited efficiencies at high
cell densities, so that the loss of the expressed materials in the
filter beds themselves can be up to 5% of the materials produced by
the bioreactor. The use of mammalian cell cultures including
Chinese hamster ovary (CHO), NS0 hybridoma cells, baby hamster
kidney (BHK) cells, insect cells, and human cells (e.g. T-cells,
B-cells, stem cells, red blood cells), and living/biological cells
in general has proven to be a very efficacious way of
producing/expressing the recombinant proteins and monoclonal
antibodies used with today's pharmaceuticals. The filtration of the
mammalian cells and the mammalian cell debris through
acoustophoresis aids in greatly increasing the yield of the
bioreactor. As desired, the acoustophoresis process may also be
coupled with a standard filtration process upstream or downstream,
such as depth filtration, tangential flow filtration (TFF), or
other physical filtration processes.
[0064] In this regard, the acoustic contrast factor is a function
of the ratio of particle to fluid compressibility and particle to
fluid density. Most cell types present a higher density and lower
compressibility than the medium in which they are suspended, so
that the acoustic contrast factor between the cells and the medium
has a positive value. As a result, the axial acoustic radiation
force (ARF) drives the cells, with a positive contrast factor, to
the pressure nodal planes, whereas cells or other particles with a
negative contrast factor are driven to the pressure anti-nodal
planes. The radial or lateral component of the ARF is larger than
the combined effect of fluid drag force and gravitational force.
The radial or lateral component drives the cells/particles to
specific locations (points) within these planes where they cluster,
clump, agglomerate, or coalesce into larger groups, which will then
continuously gravity separate from the fluid.
[0065] Desirably, the ultrasonic transducer(s) generate a
three-dimensional or multi-dimensional acoustic standing wave in
the fluid that exerts a lateral force on the suspended particles to
accompany the axial force so as to increase the particle trapping
and clumping capabilities of the standing wave. Typical results
published in literature state that the lateral force is two orders
of magnitude smaller than the axial force. In contrast, the
technology disclosed in this application provides for a lateral
force to be of the same order of magnitude as the axial force (i.e.
a multi-dimensional acoustic standing wave). However, in certain
embodiments described further herein, combinations of transducers
that produce both multi-dimensional acoustic standing waves and
planar standing waves are contemplated. For purposes of this
disclosure, a standing wave where the lateral force is of the same
order of magnitude as the axial force is considered a
"multi-dimensional acoustic standing wave."
[0066] It may be necessary, at times, due to acoustic streaming, to
modulate the frequency or voltage amplitude of the standing wave.
This may be done by amplitude modulation and/or by frequency
modulation. The duty cycle of the propagation of the standing wave
may also be utilized to achieve certain results for trapping of
materials. In other words, the acoustic beam may be turned on and
shut off at different frequencies to achieve desired results.
[0067] A diagrammatic representation of an embodiment for removing
oil or other lighter-than-water material is shown in FIG. 5.
Excitation frequencies typically in the range from hundreds of kHz
to 10 s of MHz are applied by transducer 10. One or more standing
waves are created between the transducer 10 and the reflector 11.
In some configurations, reflector 11 can be implemented as an
acoustic transducer, similar to or different from transducer 10, to
form the acoustic standing waves there between. Microdroplets 12
are trapped in standing waves at the pressure anti-nodes 14 where
they agglomerate, aggregate, clump, or coalesce, and, in the case
of buoyant material, float to the surface and are discharged via an
effluent outlet 16 located above the flow path. Clarified water is
discharged at outlet 18. The acoustophoretic separation technology
can accomplish multi-component particle separation without any
fouling at a much reduced cost.
[0068] A diagrammatic representation of an embodiment for removing
contaminants or other heavier-than-water material is shown in FIG.
6. Excitation frequencies typically in the range from hundreds of
kHz to 10 s of MHz are applied by transducer 10. An acoustic wave
is generated by transducer 10 and propagates to reflector 11, which
reflects the acoustic wave to create an acoustic standing wave.
Reflector 11 can be implemented as an acoustic transducer, similar
to or different from transducer 10, and can be actuated to
contribute to generating an acoustic standing wave in conjunction
with transducer 10. Contaminants in the incoming water 13 are
trapped in standing waves at the pressure nodes 15 where they
agglomerate, aggregate, clump, or coalesce, and, in the case of
heavier material, sink to the bottom collector and are discharged
via an effluent outlet 17 located below the flow path. Clarified
water is discharged at outlet 18.
[0069] As previously explained, the ultrasonic transducer and
reflector are located on opposite sides of the acoustic chamber. In
this way, one or more acoustic standing waves are created between
the ultrasonic transducer and reflector.
[0070] Prior to discussing further optimization of the systems, it
is helpful to provide an explanation now of how multi-dimensional
acoustic standing waves are generated. The multi-dimensional
acoustic standing wave needed for particle collection is obtained
by driving an ultrasonic transducer at a frequency that both
generates the acoustic standing wave and excites a fundamental 3D
vibration mode of the transducer piezoelectric element.
Perturbation of the piezoelectric element in an ultrasonic
transducer in a multimode fashion allows for generation of a
multidimensional acoustic standing wave. A piezoelectric element
can be specifically designed to deform in a multimode fashion at
designed frequencies, allowing for generation of a
multi-dimensional acoustic standing wave. The multi-dimensional
acoustic standing wave may be generated by distinct modes of the
piezoelectric element such as a 3.times.3 mode that would generate
multidimensional acoustic standing waves. A multitude of
multidimensional acoustic standing waves may also be generated by
allowing the piezoelectric element to vibrate through many
different mode shapes. Thus, the element would excite multiple
modes such as a 0.times.0 mode (i.e. a piston mode) to a 1.times.1
(the fundamental mode), to 2.times.2, 1.times.3, 3.times.1,
3.times.3, and other higher order modes and then cycle back through
the lower modes of the element (not necessarily in straight order).
This switching or dithering of the piezoelectric element between
modes allows for various multi-dimensional wave shapes, along with
a single piston mode shape, to be generated over a designated
time.
[0071] It is also possible to excite or choose a frequency of
excitation that excites multiple modes at the same time, each mode
with a varying degree of displacement amplitude. Through this
combination of multiple modes excited at the same time with varying
displacement amplitude, it is possible to generate a superposition
of multi-dimensional standing waves desirable for trapping,
clustering, and separation of a secondary fluid or particle from a
host fluid.
[0072] The scattering of the acoustic field off the particles
results in a three dimensional acoustic radiation force, which acts
as a three-dimensional trapping field. The acoustic radiation force
is proportional to the particle volume (e.g. the cube of the
radius) when the particle is small relative to the wavelength. It
is proportional to frequency and the acoustic contrast factor. It
also scales with acoustic energy (e.g. the square of the acoustic
pressure amplitude). When the acoustic radiation force exerted on
the particles is stronger than the combined effect of fluid drag
force and buoyancy and gravitational force, the particles are
trapped within the acoustic standing wave field. This results in
concentration, agglomeration and/or coalescence of the trapped
particles. Relatively large solids of one material can thus be
separated from smaller particles of a different material, the same
material, and/or the host fluid through enhanced gravitational
separation.
[0073] The multi-dimensional standing wave generates acoustic
radiation forces in both the axial direction (i.e., in the
direction of the standing wave, between the transducer and the
reflector, perpendicular to the flow direction) and the lateral
direction (i.e., in the flow direction). As the mixture flows
through the acoustic chamber, particles in suspension experience a
strong axial force component in the direction of the standing wave.
Since this acoustic force is perpendicular to the flow direction
and the drag force, it quickly moves the particles to pressure
nodal planes or anti-nodal planes, depending on the contrast factor
of the particle. The lateral acoustic radiation force then acts to
move the concentrated particles towards the center of each planar
node, resulting in agglomeration or clumping. The lateral acoustic
radiation force component may overcome fluid drag for such clumps
of particles to continually grow and then drop out of the mixture
due to gravity. Therefore, both the drop in drag per particle as
the particle cluster increases in size, as well as the drop in
acoustic radiation force per particle as the particle cluster grows
in size, may be considered for operation of the acoustic separator
device. In the present disclosure, the lateral force component and
the axial force component of the multi-dimensional acoustic
standing wave are of the same order of magnitude. In this regard,
it is noted that in a multi-dimensional acoustic standing wave, the
axial force is stronger than the lateral force, but the lateral
force of a multi-dimensional acoustic standing wave is much higher
than the lateral force of a planar standing wave, usually by two
orders of magnitude or more.
[0074] Some further explanation of the ultrasonic transducers used
in the devices, systems, and methods of the present disclosure may
be helpful as well. In this regard, the transducers use a
piezoelectric element, usually made of PZT-8 (lead zirconate
titanate). Such elements may have a 1 inch cross-section and a
nominal 2 MHz resonance frequency, and may also be of a larger
size. Each ultrasonic transducer module can have only one
piezoelectric element, or can have multiple elements that each act
as a separate ultrasonic transducer and are either controlled by
one or multiple amplifiers. The piezoelectric element(s) can be
crystalline, semi-crystalline, or non-crystalline. The
piezoelectric element(s) can be square, rectangular, irregular
polygon, or generally of any arbitrary shape. The transducer(s)
is/are used to create a pressure field that generates forces of the
same order of magnitude both orthogonal to the standing wave
direction (lateral) and in the standing wave direction (axial).
[0075] FIG. 7 is a cross-sectional diagram of a conventional
ultrasonic transducer. This transducer has a wear plate 50 at a
bottom end, epoxy layer 52, piezoelectric element 54 (e.g. a
ceramic crystal made of, e.g. PZT), an epoxy layer 56, and a
backing layer 58. On either side of the piezoelectric element,
there is an electrode: a positive electrode 61 and a negative
electrode 63. The epoxy layer 56 attaches backing layer 58 to the
piezoelectric element 54. The entire assembly is contained in a
housing 60 which may be made out of, for example, aluminum. An
electrical adapter 62 provides connection for wires to pass through
the housing and connect to leads (not shown) which attach to the
piezoelectric element 54. Typically, backing layers are designed to
add damping and to create a broadband transducer with uniform
displacement across a wide range of frequency and are designed to
suppress excitation at particular vibrational eigen-modes. Wear
plates are usually designed as impedance transformers to better
match the characteristic impedance of the medium into which the
transducer radiates.
[0076] FIG. 8 is a cross-sectional view of an ultrasonic transducer
81 of the present disclosure. Transducer 81 is shaped as a disc or
a plate, and has an aluminum housing 82. The piezoelectric element
can be, e.g., a mass of perovskite ceramic crystals, each
consisting of a small, tetravalent metal ion, usually titanium or
zirconium, in a lattice of larger, divalent metal ions, usually
lead or barium, and O2- ions. As an example, in the embodiment
shown in FIG. 8, a PZT (lead zirconate titanate) crystal 86 defines
the bottom end of the transducer, and is exposed from the exterior
of the housing. The crystal is supported on its perimeter by a
small elastic layer 98, e.g. silicone or similar material, located
between the crystal and the housing. Put another way, no wear layer
is present. In particular embodiments, the crystal is an irregular
polygon, and in further embodiments is an asymmetrical irregular
polygon.
[0077] Screws 88 attach an aluminum top plate 82a of the housing to
the body 82b of the housing via threads. The top plate includes a
connector 84 for powering the transducer. The top surface of the
PZT crystal 86 is connected to a positive electrode 90 and a
negative electrode 92, which are separated by an insulating
material 94. The electrodes can be made from any conductive
material, such as silver or nickel. Electrical power is provided to
the PZT crystal 86 through the electrodes on the crystal. Note that
the crystal 86 has no backing layer or epoxy layer. Put another
way, there is an air gap 87 in the transducer between aluminum top
plate 82a and the crystal 86 (i.e. the air gap is completely
empty). A minimal backing 58 and/or wear plate 50 may be provided
in some embodiments, as seen in FIG. 9.
[0078] The transducer design can affect performance of the system.
A typical transducer is a layered structure with the piezoelectric
element bonded to a backing layer and a wear plate. Because the
transducer is loaded with the high mechanical impedance presented
by the standing wave, the traditional design guidelines for wear
plates, e.g., half wavelength thickness for standing wave
applications or quarter wavelength thickness for radiation
applications, and manufacturing methods may not be appropriate.
Rather, in one embodiment of the present disclosure the
transducers, there is no wear plate or backing, allowing the
piezoelectric element to vibrate in one of its eigenmodes (i.e.
near eigenfrequency) with a high Q-factor. The vibrating
piezoelectric element, such as, e.g., a ceramic crystal/disk, is
directly exposed to the fluid flowing through the acoustic
chamber.
[0079] Removing the backing (e.g. making the piezoelectric element
air backed) also permits the element to vibrate at higher order
modes of vibration with little damping (e.g. higher order modal
displacement). In a transducer having a piezoelectric element with
a backing, the element vibrates with a more uniform displacement,
like a piston. Removing the backing allows the element to vibrate
in a non-uniform displacement mode. The higher order the mode shape
of the piezoelectric element, the more nodal lines the element has.
The higher order modal displacement of the element creates more
trapping lines, although the correlation of trapping line to node
is not necessarily one to one, and driving the element at a higher
frequency will not necessarily produce more trapping lines.
[0080] In some embodiments, the piezoelectric element may have a
backing that minimally affects the Q-factor of the crystal (e.g.
less than 5%). The backing may be made of a substantially
acoustically transparent material such as balsa wood, foam, or cork
which allows the element to vibrate in a higher order mode shape
and maintains a high Q-factor while still providing some mechanical
support for the element. The backing layer may be a solid, or may
be a lattice having holes through the layer, such that the lattice
follows the nodes of the vibrating element in a particular higher
order vibration mode, providing support at node locations while
allowing the rest of the element to vibrate freely. The goal of the
lattice work or acoustically transparent material is to provide
support without lowering the Q-factor of the piezoelectric element
or interfering with the excitation of a particular mode shape.
[0081] Placing the piezoelectric element in direct contact with the
fluid also contributes to the high Q-factor by avoiding the
dampening and energy absorption effects of the epoxy layer and the
wear plate. Other embodiments may have wear plates or a wear
surface to prevent the PZT, which contains lead, contacting the
host fluid. This may be desirable in, for example, biological
applications such as separating blood. Such applications might use
a wear layer such as chrome, electrolytic nickel, or electroless
nickel. Chemical vapor deposition could also be used to apply a
layer of poly(p-xylylene) (e.g. Parylene) or other polymers or
polymer films. Organic and biocompatible coatings such as silicone
or polyurethane are also usable as a wear surface.
[0082] Perturbation of the piezoelectric element in an ultrasonic
transducer in a multimode fashion allows for generation of a
multi-dimensional acoustic standing wave. A piezoelectric element
can be specifically designed to deform in a multi-mode fashion at
designed frequencies, allowing for generation of a
multi-dimensional acoustic standing wave. The multi-dimensional
acoustic standing wave may be generated by distinct modes of the
piezoelectric element such as the 3.times.3 mode that would
generate multi-dimensional acoustic standing waves. A multitude of
multi-dimensional acoustic standing waves may also be generated by
allowing the piezoelectric element to vibrate through many
different mode shapes by changing frequency over a small interval.
Thus, the piezoelectric element would excite multiple modes such as
a 0.times.0 mode (i.e. a piston mode) to a 1.times.1, 2.times.2,
1.times.3, 3.times.1, 3.times.3, and other higher order modes and
then cycle back through the lower modes of the piezoelectric
element (not necessarily in straight order). This switching or
dithering of the piezoelectric element between modes allows for
various multi-dimensional wave shapes, along with a single piston
mode shape, to be generated over a designated time. In other
embodiments, the excitation is a fixed frequency excitation where a
weighted combination of several modes contribute to the overall
displacement profile of the piezoelectric element. The lateral
force of the total acoustic radiation force (ARF) generated by the
ultrasonic transducers of the present disclosure is significant and
is sufficient to overcome the fluid drag force at high linear
velocities up to 1 cm/s and beyond. For example, linear velocities
through the devices of the present disclosure can be a minimum of 4
cm/min for separation of cells/particles, and can be as high as 1
cm/sec for separation of oil/water phases.
[0083] The lateral force of the acoustic radiation force generated
by the transducer can be increased by driving the transducer in
higher order mode shapes, as opposed to a form of vibration where
the piezoelectric element effectively moves as a piston having a
uniform displacement. The acoustic pressure is proportional to the
driving voltage of the transducer. The electrical power is
proportional to the square of the voltage. The transducer is
typically a thin piezoelectric plate, with electric field in the
z-axis and primary displacement in the z-axis. The transducer is
typically coupled on one side by air (i.e., the air gap within the
transducer) and on the other side by the fluid mixture of the cell
culture media. The types of waves generated in the plate are known
as composite waves. A subset of composite waves in the
piezoelectric plate is similar to leaky symmetric (also referred to
as compressional or extensional) Lamb waves. The piezoelectric
nature of the plate typically results in the excitation of
symmetric Lamb waves. The waves are leaky because they radiate into
the water layer, which result in the generation of the acoustic
standing waves in the water layer. Lamb waves exist in thin plates
of infinite extent with stress free conditions on its surfaces.
Because the transducers of this embodiment are finite in nature,
the actual modal displacements are more complicated.
[0084] FIG. 10 shows the typical variation of the in-plane
displacement (x-displacement) and out-of-plane displacement
(y-displacement) across the thickness of the plate, the in-plane
displacement being an even function across the thickness of the
plate and the out-of-plane displacement being an odd function.
Because of the finite size of the plate, the displacement
components vary across the width and length of the plate. In
general, a (m,n) mode is a displacement mode of the transducer in
which there are m undulations in transducer displacement in the
width direction and n undulations in the length direction, and with
the thickness variation, as described in FIG. 10. The maximum
number of m and n is a function of the dimension of the
piezoelectric element and the frequency of excitation. Additional
three-dimensional modes exist that are not of the form (m,n).
[0085] The transducers are driven so that the piezoelectric element
vibrates in higher order modes of the general formula (m, n), where
m and n are independently 1 or greater. In particular embodiments,
the piezoelectric element vibrates in at least three modes: modes
(1, 1); (1, 3); and (3, 3). Higher order modes will produce more
nodes and antinodes, result in three-dimensional standing waves in
the water layer, characterized by strong gradients in the acoustic
field in all directions, not only in the direction of the standing
waves, but also in the lateral directions. As a consequence, the
acoustic gradients result in stronger trapping forces in the
lateral direction.
[0086] FIG. 11 presents analytical results for the displacement
response of a 25.4.times.25.4.times.1 mm PZT-8 piezoelectric
crystal radiating into a semi-infinite water layer. The crystal was
driven in three different (m, n) modes: Mode 11 (1, 1), Mode 13 (1,
3), and Mode 33 (3, 3). In FIG. 11, the uppermost line represents
the sum of all three modes, the upper middle line represents Mode
11, the lower middle line represents Mode 13, and the lowermost
line represents Mode 33. As can be seen in FIG. 11, there is little
impact on the total displacement of the piezoelectric crystal in
the poling direction. When the piezoelectric element radiates into
a water layer, its displacement profile is mostly that of the
fundamental mode. The displacement amplitude of the higher order
modes are smaller across the entire frequency range of interest and
thereby have minimal effect on the generation of the radiated
acoustic wave. Note also that the resonance frequencies of the
higher order modes increase with mode number.
[0087] FIG. 12 presents analytical results for the displacement
response of a 25.4.times.25.4.times.1 mm PZT-8 piezoelectric
crystal with a 25.4 mm fluid chamber terminated by a rigid acoustic
reflector. Again, the crystal was driven in three different (m, n)
modes: Mode 11 (1, 1), Mode 13 (1, 3), and Mode 33 (3, 3). In FIG.
12, the uppermost line represents the sum of all three modes, the
upper middle line represents Mode 11, the lower middle line
represents Mode 13, and the lowermost line represents Mode 33. As
can be seen by comparing FIG. 12 with FIG. 11, in FIG. 12 there are
multiple modes with similar orders of magnitude of displacement of
the piezoelectric crystal in the poling direction. Put another way,
the fundamental mode (1, 1) is no longer dominant at all
frequencies. For some frequencies of excitation, the (1, 3) mode is
dominant, while the (3, 3) mode is dominant for another frequency.
For other frequencies, the strength of several modes are similar,
and therefore all contribute to the overall displacement profile,
which is then a superposition of each of the modes. It should be
noted that the peaks in displacement of the three modes overlap
each other at roughly equivalent frequencies in the region of
higher frequencies. The peaks in each mode are roughly within 0.005
megahertz (MHz) of each other.
[0088] Based on these analytical results, a numerical model was
developed using the piezoelectric equations described above. In
FIG. 13, this numerical model is represented in a two-dimensional
COMSOL model in which the piezoelectric crystal(s) were operated at
a frequency of 2.235 MHz. In FIG. 13, the y-axis represents the
height of the system in inches and the x-axis represents the width
of the system in inches. The two labels of the graph represent
total displacement of the piezoelectric crystal in inches (right
most label), and the inner label represents the acoustic potential
(U). As can be seen in FIG. 13, the generation of a
multi-dimensional acoustic standing wave creates multiple lines of
acoustic potential minima.
[0089] FIG. 14 and FIG. 15 present these numerical results. More
specifically, FIG. 14 presents numerical results for the
displacement response of a 25.4.times.25.4.times.1 mm PZT-8
piezoelectric crystal with a 25.4 mm fluid chamber. As can be seen
in FIG. 14, the displacement profile has multiple peaks across the
range of operating frequencies. For a 25.4 mm fluid layer, the
planar acoustic resonance frequency spacing is about 29 kHz. The
additional peaks seen in FIG. 15 are indications of the action of
the higher order modes, similar to the predictions of the
theoretical model. FIG. 15 presents numerical results for the
current response of a 25.4.times.25.4.times.1 mm PZT-8
piezoelectric crystal with a 25.4 mm fluid chamber. As can be seen
by comparing FIG. 15 with FIG. 14, the current response shows
similar behavior to the displacement response, insofar as the
current response has multiple peaks across the range of operating
frequencies.
[0090] In embodiments, the voltage signal driving the transducer
can have a sinusoidal, square, sawtooth, pulsed, or triangle
waveform; and have a frequency of 500 kHz to 10 MHz. The voltage
signal can be driven with pulse width modulation, which produces
any desired waveform. The voltage signal can also have amplitude or
frequency modulation start/stop capability to eliminate streaming.
In one experimental setup shown in FIG. 16, a 30 kHz sweep was
used, and the current response was plotted versus frequency,
similar to FIG. 15. As seen in FIG. 16, multiple resonance peaks
were found to exist, showing that the experimental results confirm
both the theoretical and numerical results.
[0091] The transducers are used to create a pressure field that
generates acoustic radiation forces of the same order of magnitude
both orthogonal to the standing wave direction and in the standing
wave direction. When the forces are roughly the same order of
magnitude, particles of size 0.1 microns to 300 microns will be
moved more effectively towards "trapping lines," so that the
particles will not pass through the pressure field. Instead, the
particles will remain within the acoustic chamber, from which they
can advantageously be collected via specified outlets of the
acoustophoretic device or otherwise recycled back to an associated
bioreactor.
[0092] The acoustophoretic devices and methods described herein are
useful for separating a second fluid or particulate from a host
fluid. In this regard, the devices and methods of the present
disclosure utilize higher order modal displacement of a
piezoelectric element, with multiple modes having the same order of
magnitude, which allows for stronger and more efficient trapping of
the second fluid or particulate.
[0093] The present disclosure has been described with reference to
exemplary embodiments. Modifications and alterations may occur to
others upon reading and understanding the preceding detailed
description. It is intended that the present disclosure be
construed as including all such modifications and alterations
insofar as they come within the scope of the appended claims or the
equivalents thereof.
* * * * *